Lyme disease is the most common vector-borne disease in the United States. It is caused by the spirochete, Borrelia burgdorferi, and is transmitted to humans in the northeast United States by Ixodes dammini, the northern deer tick. Worldwide, these and other Ixodid ticks are the most important hematophagous arthropod vectors of infectious diseases to animals and second in importance, to mosquitos, as vectors of infectious pathogens to humans. Studies have demonstrated that tick bites are difficult to recognize and often go unrecognized. This inability to recognize tick bites is a hindrance to the prevention of the disease and to its epidemiologic investigation. Biological markers of exposure to ticks would thus have utility in epidemiologic studies of risk factors for Lyme disease and in the prevention of the disease. A large body of literature documents that hosts develop complex immunologic reactions to ticks; it has been demonstrated that laboratory animals produce antibodies to several components of I. dammini saliva and recent studies suggest that human antibodies to tick salivary gland proteins may be a useful biological marker of exposure to ticks. The overall goal of this proposal is to validate a biological marker of tick exposure, anti-tick salivary gland protein antibody (ATA) in human serum, and to show the utility of such a marker in epidemiologic studies of Lyme disease. Several field-based epidemiologic studies, and laboratory experiments aimed at optimizing ELISA conditions for the assays and identifying specific protein components of I. dammini saliva that elicit antibody response, are included. The goals of the field-based studies are to establish the sensitivity, specificity, and positive predictive value of ATA in workers presenting with a recent tick bite, follow the time course of development of ATA in such workers (kinetics), examine the individual variability of human responses to the antigen, and evaluate the use of ATA as an outcome measure (dependent variable) of tick exposure, first in observational epidemiologic studies, then in a randomized controlled trial of permethrin in outdoor workers.